We have conducted trials with retinoids in human cancers and detected and reported major activity against the cutaneous T- cell lymphoma mycosis fungoides, laryngeal papillomatosis, and advanced squamous/basal cell carcinoma of the skin. Additionally, responses of cervical dysplasia, head and neck cancers, myelodysplastic syndromes, and melanoma have been documented. Based on these observations, we plan to expand certain of these observations to include: a phase II trial of 13cRA plus rIFN-alpha A for mycosis fungoides, a randomized phase II study of rIFN-alpha A + 13cRA or rIFN-alpha A for metastatic melanoma, and a dedicated phase II trial of 13cRA for advanced or metastatic squamous/basal cell carcinoma of the skin. New directions include a phase II trial of 13cRA in patients with the preneoplastic condition Barrett's esophagus, a randomized phase II trial of 13cRA or beta-carotene for oral leukoplakia, and a phase II trial of 13cRA for laryngeal dysplasia. The project has enhanced considerably our knowledge of the role of retinoids in preneoplastic and neoplastic conditions and the current proposal will deepen and expand that effort.